Kennedy et al.

Journal of Foot and Ankle Research (2020) 13:10

https://doi.org/10.1186/s13047-020-0378-2

REVIEW Open Access

Walking and weakness in children: a

narrative review of gait and functional
ambulation in paediatric neuromuscular
disease
Rachel A. Kennedy1,2,3* , Kate Carroll1,2,3, Jennifer L. McGinley2,3 and Kade L. Paterson3

Abstract
Background: Weakness is the primary impairment in paediatric neuromuscular diseases, impacting gait and gait-
related functional activities in ambulant children affected by these rare and often degenerative diseases. Gait speed
is an indicator of health and disability, yet gait is a complex, multi-faceted activity. Using the International
Classification of Function, Health and Disability (ICF) model, assessment of gait and functional ambulation should
consider the impairments, activity limitations and participation restrictions due to disease, and factors related to the
environment and the individual person.
Methods: This narrative review involved a literature search of databases including Medline, Embase and Pubmed
from 1946 to October 2019. Inclusion criteria included assessments of gait, endurance and ambulatory function in
paediatric (0–18 years) neuromuscular diseases.
Results: Fifty-two papers were identified reporting assessments of gait speed, timed function, endurance and
ambulatory capacity, gait-related balance and qualitative descriptive assessments of gait function and effect of
disease on gait and gait-related activities. Gait speed is an indicator of disability and children with neuromuscular
disease walk slower than typically developing peers. Increasing disease severity and age were associated with
slower walking in children with Duchenne muscular dystrophy and Charcot-Marie-Tooth disease. The six-minute
walk test is used widely as a test of endurance and ambulatory capacity; six-minute walk distance was substantially
reduced across all paediatric neuromuscular diseases. Endurance and ambulatory capacity was more limited in
children with spinal muscular atrophy type 3, congenital muscular dystrophy and older boys with Duchenne
muscular dystrophy. Only a few papers considered normalisation of gait parameters accounting for the effect on
gait of height in heterogeneous groups of children and linear growth in longitudinal studies. Balance related to gait
was considered in five papers, mainly in children with Charcot-Marie-Tooth disease. There was limited investigation
of factors including distance requirements and terrain in children’s typical environments and personal factors
related to self-perception of disease effect on gait and gait-related function.
(Continued on next page)

* Correspondence: rachel.kennedy@rch.org.au
1
Department of Neurology, The Royal Children’s Hospital, Parkville, Vic,
Australia
2
Murdoch Children’s Research Institute, Parkville, Vic, Australia
Full list of author information is available at the end of the article

© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Kennedy et al. Journal of Foot and Ankle Research (2020) 13:10 Page 2 of 15

(Continued from previous page)

Conclusion: Assessments of gait and functional ambulation are important considerations in documenting disease
progression and treatment efficacy in the clinical setting; and in clinical trials of disease-modifying agents and
physiotherapeutic interventions in paediatric neuromuscular diseases. There is a need for expert consensus on core
gait and functional ambulation assessments for use in clinical and research settings.
Keywords: Neuromuscular disease, Duchenne muscular dystrophy, Spinal muscular atrophy, Charcot-Marie-tooth
disease, Myopathy, Weakness, Paediatric, Gait, Functional ambulation, Assessment

Background frequent trips and falls, increased fatigue and difficulty

Neuromuscular diseases (NMD) include disorders affect-
ing the anterior horn cells, peripheral nerves, neuromus-
cular junction and muscles, are often progressive and
exhibit a wide range of impairment and disability in af-
fected individuals. Relatively rare, in children these dis-
eases include spinal muscular atrophy (SMA; 1 in 10–
11,000) [1], Charcot-Marie-Tooth disease (CMT; 1 in
2.5–10,000) [2] and Duchenne muscular dystrophy
(DMD; 1 in 3.5–10,0000) [3]. Gait and functional ambu-
lation are important markers of disease and disability in
paediatric NMD. It has been proposed that gait velocity
or self-selected walking speed is the 6th vital sign of hu-
man function and is a predictor of overall health and
disability [4, 5]. Yet, human gait is a complex activity
and gait speed alone does not reflect all contributing fac-
tors and influences on gait [4, 5]. Functional ambulation
relates gait function and speed to mobility-related activ-
ities of daily living in a person’s own environment [6].
Thus, the assessment of gait and functional ambulation
in paediatric NMD must take in to consideration the
many constructs that contribute to these complex tasks,
including individual impairments, the task required, and
the environment in which these are performed.
Weakness is the primary impairment in NMD, often
presenting in childhood and adversely affecting gait and
functional ambulation. Additionally, muscle tightness,
contracture, musculoskeletal deformities, poor standing
balance and reduced endurance, all arising from weakness,
affect functional ambulatory tasks such as standing and
walking. Patterns of weakness differ depending on the
NMD, some affecting more proximal muscles (e.g. DMD)
and others more distal muscles (e.g. CMT). For the major-
ity of NMD of childhood, disease is progressive leading to
increasing weakness and disability across the lifespan. The
degree of disability in childhood NMD is variable ranging
from children who are extremely weak and unable to sit
(e.g. SMA type 1) to those with milder weakness who re-
main ambulant, albeit with gait difficulties including foot
drop, poor balance and reduced gait speed (e.g. CMT,
SMA type 3 and ambulant boys with DMD).
Gait dysfunction has important implications for func-
tion in everyday life. Ambulant children with NMD,
commonly report problems with walking, poor balance,
keeping up with peers [7–11]. In this context, it is useful
to consider the assessment of gait and functional ambu-
lation in ambulant children with NMD in terms of the
International Classification of Function, Health and Dis-
ability (ICF) [12] (Fig. 1). Gait speed is an indicator of
impairment. However, a clinically meaningful assess-
ment also needs to consider limitations to the child’s ac-
tivities, restrictions to participation, environmental and
intrinsic personal factors. Activity limitations may in-
clude difficulty walking longer distances; problems with
balance may affect steadiness and safety when walking;
and ambulatory performance may be affected by changes
in environmental conditions, for example walking over
uneven ground or up and down steps. The use of gait or
mobility aids will also affect function and low walking
confidence or fear of falling may restrict participation
opportunities. Assessments of functional ambulation
need to take into account all of these factors. There is
no recognised single assessment tool of functional am-
bulation that encompasses all factors. However, there
are several clinical assessments that collectively illustrate
the effect of disease and disability on gait and function
in children with NMD. The aim of this paper is to re-
view assessments of gait and functional ambulation in
paediatric NMD.
Method
This narrative review considered the literature relating to
gait and functional ambulation in children and adolescents
with neuromuscular disease. Literature was searched in
Ovid Medline, Embase and PubMed from 1946 up to and
including October 2019. Keywords and search terms in-
cluded gait, walk*, ambul*, locomotion, functional ambul*,
paed*, pediatr*, child*, adoles*, neuromuscular disease,
Duchenne and Becker muscular dystrophy, Charcot-
Marie-Tooth disease, peripheral neuropathy not diabetes,
spinal muscular atrophy, myopathy, Pompe, myotonic
dystrophy, collagen VI disorders, fascioscapulohumeral
dystrophy or FSHD. Only full-text human studies in Eng-
lish were considered (see Supplementary material for ex-
ample of search strategy). Additionally, hand searching of
reference lists and conference abstracts was undertaken to
ensure relevant publications were included. Exclusion
Kennedy et al. Journal of Foot and Ankle Research (2020) 13:10
Fig. 1 Paediatric neuromuscular disease as it relates to the ICF – factors relating to gait and functional ambulation (bold)
criteria included studies of non-ambulant participants, pri-
mary studies of physical activity and activity monitoring
that did not include assessments of gait or functional am-
bulation, and studies comprised primarily of adults (aged
> 18 years).
Results and discussion
Studies included
Review of the literature resulted in 52 papers describing
gait and functional ambulation in over eight neuromus-
cular diseases of childhood including CMT (15 papers),
Becker and Duchenne muscular dystrophies (B/DMD)
(21 papers), SMA (7 papers), congenital myotonic dys-
trophy (CMD) (2 papers), fascioscapulohumeral dys-
trophy (FSHD) (1 paper), Pompe disease (1 paper),
collagen VI disorders (1 paper) and other mixed cohorts
(4 papers) (Table 1). Two papers were systematic reviews
of gait in CMT [18] and DMD [28]. Several papers de-
scribed the same or similar cohorts, either cross-sectional
and longitudinal studies [11, 16, 20, 21, 34, 35, 42] or a de-
scriptive papers of a randomised controlled trial (RCT)
[24, 25, 38, 39]. The median age of participants in the
studies was 9.0 years and sample sizes ranged from 4 to
520. Some studies included adult participants and were
Page 3 of 15
included despite the lack of age-related sub-analysis [9, 10,
26, 36, 48–52, 56, 57, 60] or if there were no paediatric
studies in a specific disease [55].
Assessments of gait and functional ambulation
Several assessments of gait and functional ambulation in
paediatric NMD were identified and discussed in the lit-
erature. These included timed function tests, for ex-
ample the 10 m walk and/or run test [62, 63], the six-
minute walk test (6MWT) [64] and 100 m timed test
[30]. Tests of dynamic balance in walking, including the
balance subset of the Bruininks-Oseretsky Test, 2nd edi-
tion (BOT-2) [65] and the timed up and go (TUG) [66],
were considered due to the impact of balance on gait
and function. If studies of gait or functional ambulation
included activity monitoring, these were reported as an
adjunct to specific assessments of gait, however we did
not specifically search for studies of activity monitoring
alone. We also included descriptive scales or question-
naires that characterised gait-related function, including
the Functional Mobility Scale (FMS) [67] and the Walk-
12 scale [68].
Table 1 Review papers including disease, author, study type, sample age and size, outcome measures and main findings
Disease Study type Sample size Age Outcome measures Gait speed 6MWD 10 m walk/run Other assessments
Author years m/s m s
mean (SD) mean (SD) mean (SD) mean (SD)
CMT Cross-sectional, CMT n = 520 10.9 (4.4) Balance (BOT-2) ↓ balance
observational Mean (SD)
z-score − 3.25 (2.9)
Estilow et al. 2019 [13]
Cross-sectional, case- CMT n = 50 CMT 12.5 (3.9) 6MWT ↓ 6MWD ↓ balance (BOT-2 /37)
controlled observational TD n = 50 TD 12.5 (3.9) Balance (BOT-2)Walk- CMT 507.7 (137.3) median (IQR)
Kennedy et al. 2019 [14] 12 TD 643.3 (75.6); CMT 19 (9)
p < 0.001 TD 32 (3)
Norm to height p < 0.001
CMT 341.9 (95.7) Walk-12 mean score 24.7%
TD 429.4 (56.0); (SD 19) 95% CI [19.3, 30.2]
p < 0.001 n = 49
Longitudinal observational CMT n = 40 CMT 11.45 (3.50) 10 m walk test Slower 10 m walk
Baptista et al. 2019 [15] TD n = 49 TD 10.62 (3.10) (baseline) Median (25th; 75th)
Kennedy et al. Journal of Foot and Ankle Research

CMT 7.90 (6.67;8.92)

TD 7.25 (5.60; 8.56);
p ≤ 0.05
Cross-sectional, case- CMT n = 30 CMT 11.5 (3.7) Gait speed Slower speed ↓ 6MWD Slower 10 m ↓ balance (BOT-2 /37)
controlled observational TD n = 30 TD 11.5 (3.7) 6MWT CMT 1.19 (0.16) CMT 557 (73) walk/run Median (IQR)
Kennedy et al. 2018 [11] b1 10 m walk/run (n = 26) TD 1.32 (0.14); TD 615 (71); CMT 3.8 (1.0) CMT 25.5 (4–34)
Balance (BOT-2) p < 0.001 p < 0.001 TD 2.9 (0.3); TD 32 (26–35)
(2020) 13:10

p < 0.001 p < 0.001

Longitudinal cohort CMT n = 27 Baseline 11.1 Gait speed non−/norm Slower norm speed ↓ norm 6MWD over No change in balance over
Kennedy et al. (3.7) 6MWT non−/norm over 12 months 12 months 12 months (BOT-2 /37)
2017 [16] b1 12 months 12.2 Balance (BOT-2) Baseline 1.18 (0.16) Baseline 556 (73.7) Baseline 22.6 (9.4)
(3.7) Functional mobility 12 months 1.15 (0.14); 12 months 555 (80.2); 12 months 23.3 (8.7)
scale (FMS) p = 0.22 p = 0.91 p = 0.76
Baseline 0.43 (0.07) Baseline 720 (117) FMS 78% reported reduced
12 months 0.41 (0.05); p = 0.04 12 months 690 (121); p = 0.006 ambulatory function
Cross-sectional, CMT n = 520 10.9 (4.4) 6MWT ↓ 6MWD in CMT
observational cohort genotypes
Cornett et al. (2016) [17] 6MWD z-scores reduced in
CMT2A, CMT1B, CMT4C
compared with CMT1A
and CMTX1;
p < 0.05
6MWD z-scores reduced
in CMT2A and CMT4C
compared with CMT1B;
p < 0.05
Systematic review 7 eligible Mean 13 Gait speed Slower speed
studies Range 2–52 Range 0.50–1.25
Kennedy et al. (2016) [18]
Cross-sectional, CMT n = 33 CMT 11.9 (3.6) Gait speed Slower speed
observational TD database TD 12.0 (3.0) dependent on gait
Ounpuu et al. (2013) [19] dysfunction
CMT toe walker 1.17
[0.21]
CMT “typical” 1.11 [0.16]a
CMT foot drop 1.03
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[0.21]a
Table 1 Review papers including disease, author, study type, sample age and size, outcome measures and main findings (Continued)
Disease Study type Sample size Age Outcome measures Gait speed 6MWD 10 m walk/run Other assessments
Author years m/s m s
mean (SD) mean (SD) mean (SD) mean (SD)
TD control 1.27 [0.11];
p < 0.001 a compared
with TD
Longitudinal Ferrarin et al. CMT n = 16 13.2 (2.9) Gait speed Non-significant
(2013) [20] b2 changes in speed
with large inter-
subject variability
Cross-sectional, case- CMT n = 21 CMT 11.9 (2.8) Gait speed Slower norm speed
controlled observational TD n = 18 yo CMT1A foot drop and
Ferrarin et al. (2012) [21] b2 TD 11.0 (3.3) yo push-off deficit 69 [9]
TD 77 [7];
p < 0.05
Norm to height
Kennedy et al. Journal of Foot and Ankle Research

Cross-sectional observational n = 21 11.9 (2.8) range Walk-12 Walk-12

Pagliano et al. (2011) [22] 6–17 Mean 12.4% (SD 9.5)
Range 0–33
RCT CMT CMT treatment Gait speed CMT treatment group
Rose et al. (2010) [23] a treatment 10 [4] yo 0.50 [0.10]
group n = 15 CMT placebo CMT placebo group
CMT placebo 11 [3] yo 0.60 [0.50]
(2020) 13:10

group n = 15
RCT n = 81 8.3 (3.5) Gait speed Baseline Baseline
Burns et al. (2009a) [24] b3 [n = 53 for 6MWT CMT treatment CMT treatment group
gait data; group 1.19 (0.16) 519 (86)
n = 65 for CMT placebo group CMT placebo group
6MWT data] 1.24 (0.19) 521 (98)
Cross-sectional, n = 81 8.3 (3.5) Gait speed CMT 2–6 yo 1.13 (0.25) CMT 2–6 yo 494.3
observational [n = 53 for 6MWT CMT 7–11 yo 1.25 (0.12) (70.6) 385–640
Burns et al. (2009b) [25] b3 gait data; CMT 12–16 yo 1.23 CMT 7–11 yo 526.8
n = 65 for (0.14) (83.1) 250–640
6MWT data] CMT 12–16 yo 518.7
(150.2) 110–710
Cross-sectional, n = 16 CMT 20.1 (13) Gait speed Slower speed
observational TD database TD 18.4 (8.5) CMT 1.12 (0.17)
a
Newman et al. (2007) [26] n = 40 TD controls 1.31 (0.13);
p < 0.001
DMD Longitudinal n = 42 7.9 (2.9) 10 m walk/run test Baseline speed 1.71 Baseline 5.85 s Significant ↓ average strides
Fowler et al. (2018) [27] Range 4.1–16.1 StepWatch Activity (0.68) m/s as measured derived from per day with ↑ age; per age
monitoring by 10 m walk/run reported gait speed group average strides per day ↑
for 4-7yo, plateau for 8-10yo
and ↓ >10yo
Systematic review of gait 9 eligible Gait speed calculated Slower speed
Goudriaan et al. (2018) [28] studies from 6 studies compared to TD
Standardised mean
difference (effect size)
ranging from 1.26
to 3.20
Page 5 of 15
Table 1 Review papers including disease, author, study type, sample age and size, outcome measures and main findings (Continued)
Disease Study type Sample size Age Outcome measures Gait speed 6MWD 10 m walk/run Other assessments
Author years m/s m s
mean (SD) mean (SD) mean (SD) mean (SD)
RCT n = 331 9.6 (1.92) 6MWT Baseline Baseline
Victor et al. (2017) [29] 10 m walk/run 329.6 (55.47) 6.8 (1.97)
Cross-sectional observational DMD n = 72 DMD range 4– 100 m timed test Slower timed 100 m across all
case controlled TD n = 599 12 ages compared to TD; p < 0.01
Alfano et al. (2017) [30] TD range 4–14 DMD times improve up to 6
years and then decline from
7 years
Cross-sectional, DMD n = 16 DMD 8.67 (2.04) Gait speed Slower speed
observational case TD n = 15 TD 9.39 (2.21) compared to TD
controlled DMD 0.78 (0.18)
Ropars et al. (2016) [31] TD 1.21 (0.13);
p < 0.001
Cross-sectional observational DMD n = 16 DMD 9.0 (2.1) 6MWT ↓ 6MWD compared to TD ↓ steps and high activity time
Kennedy et al. Journal of Foot and Ankle Research

case-controlled TD n = 13 TD 9.0 (2.4) StepWatch Activity DMD 387 (86) and ↑ inactive time compared
Davidson et al. (2015) [32] monitoring TD 598 (63); to TD
p < 0.005 Steps
DMD 5138 (2500)
TD 7239 (2621);
p = 0.044
High activity time
DMD 25 (17)
(2020) 13:10

TD 53 (34) min
p = 0.018
Inactive time
DMD 1103 (134) min
TD 1016 [33] min;
p = 0.036
Longitudinal observational n = 96 Baseline 6MWT ↓ 6MWD 3 years
Pane et al. (2014) [34] b4 8.3 (2.3) − 15.8 (77.3) at 12 months,
− 58.9 (125.7) at 24 months
and − 104.22 (146.2) at 36
months
Longitudinal observational n = 113 8.2 6MWT ↓ 6MWD 2 years
Mazzone et al. (2013) [35] b4 4.1–17.0 − 22.7 (SD 81.0) 1st year −
64.7 (SD 123.1) 2nd year
Longitudinal observational n = 340 Baseline range 10 m walk/run Slower 10 m walk/
Henricson et al. (2013a) [36] 2–28 run with ↑ age
No participant aged
> 18 years able to
walk
Longitudinal observational, DMD n = 24 DMD 7.9 (2.3) 6MWT Baseline ↓ 6MWD Baseline ↓time
case-controlled TD n = 36 TD 8.7 (2.6) 10 m walk/run DMD 369.5 (79.3) DMD 1.68 (0.56)
Henricson et al. (2013b) [37] 1 year TD 613.3 (73.6) p < 0.001 TD 3.32 (0.36)
DMD n = 13 MCID 26.4 m p < 0.001
TD n = 18 1 year change DMD > MCID 0.19 s
MCID 1 year change
DMD − 53.67 (SE 25.96) p = DMD > MCID
0.027 DMD − 0.25 (SE 0.68)
TD 16.5 (SE 11.46) p = 0.007
TD 0.33 (SE 0.07)
Page 6 of 15

p < 0.001
Table 1 Review papers including disease, author, study type, sample age and size, outcome measures and main findings (Continued)
Disease Study type Sample size Age Outcome measures Gait speed 6MWD 10 m walk/run Other assessments
Author years m/s m s
mean (SD) mean (SD) mean (SD) mean (SD)
Observational study n = 174 8.5 (2.6) 6MWT 358 (95) 7.4 (4.3)
McDonald et al. (2013a) [38] 10 m walk/run MCID 28.5–31.7 m MCID 2.3–1.4 s
Longitudinal observational n = 57 8.3 (2.33) 6MWT ↓ 6MWD 48 weeks Slower 10 m walk/
study 10 m walk/run Baseline 361.1 (87.5) run with ↑ age
McDonald et al. (2013b) [39] Week 48,317.4 (152.3) Baseline
< 7yo 4.8 (0.86)
> 7yo 7.1 (2.80)
Longitudinal observational n = 80 8.3 (2.7) 6MWT ↓ 6MWD 12 months,
study 2 genotypes associated with age
Bello et al. (2012) [40] Group 1 = 57 (r = − 0.38 p = 0.013),
Group 2 = 23 baseline
6MWD (r = 0.73, p < 0.001)
and genotype (p = 0.029)
Baseline
Kennedy et al. Journal of Foot and Ankle Research

Gp 1368 (86)
Gp 2387 (67)
12 months
Gp 1360 (98)
Gp 2343 (124)
Cross-sectional, DMD n = 15 DMD 6.1 (0.7) Gait speed Speed in younger Slower 10 m walk
observational case TD n = 9 TD 7.5 (1.2) 10 m walk boys with DMD does DMD 4.4 (3.2)
(2020) 13:10

controlled not differ to TD TD 3.4 (0.6)

Doglio et al. (2011) [41] DMD 1.06 (0.17) p < 0.05
TD 1.07 (0.18)
NS
Longitudinal observational n = 106 Baseline 10 m walk/run ↓ 6MWD 12 months, > Slower 10 m walk/
study (n = 100 10 m 8.3 (2.3) 6MWT in older boys run in older boys
Mazzone et al. (2011) [42] b4 walk/run) ≤ 7 yo − 7.8 (63.9) ≤ 7 yo 0.3 (3.1)
> 7 yo − 42.3 (73.9) > 7 yo 1.3 (3.5)
All − 25.8 (74.3); All 1.0 (3.4)
p = 0.01 p = 0.11 ≤ 7yo vs >7yo
(≤7yo vs > 7yo)
Cross-sectional observational n = 112 8.18 (2.3) 10 m walk/run Range 127–560.6 Range 3–15
study 6MWT
Mazzone et al. (2010) [43]
Cross-sectional observational DMD n = 21 Median [range] 6MWT ↓ 6MWD compared to TD
case controlled TD n = 34 DMD 8 [5–12] DMD 366 (83)
McDonald et al. (2010) [44] TD 9 [4–12] TD 621 (68);
p < 0.001
Cross-sectional observational DMD n = 11 DMD 9.2 (2.6) Gait speed Slower speed
case controlled TD n = 14 TD 9.7 (1.9) DMD 0.62 (0.12)
Gaudreault et al. (2010) [8] TD 1.02 (0.13)
p < 0.001
Cross-sectional, DMD n = 21 DMD 7.0 (2.4) Gait speed Trend to slower norm
observational case TD n = 10 TD 7.4 (1.2) speed
controlled DMD 0.81 (0.14)
D’Angelo et al. (2009) [45] TD 0.90 (0.13)
norm to height; NS
Page 7 of 15
Table 1 Review papers including disease, author, study type, sample age and size, outcome measures and main findings (Continued)
Disease Study type Sample size Age Outcome measures Gait speed 6MWD 10 m walk/run Other assessments
Author years m/s m s
mean (SD) mean (SD) mean (SD) mean (SD)
RCT n = 15 Baseline 30 ft timed walk/run Baseline 30 ft
Skura et al. (2008) [46] 8.4 (1.46) test timed run
5.6 (1.3)
RCT n = 16 Baseline 9 m run Baseline speed
Beenakker et al. (2005) [47] 6.25 (0.93) 1.78 m/s
Range 5–8 = 5.06 s over 9 m
SMA Pilot study n=4 26.2; range 10– Endurance shuttle ESWT feasible measure of
Bartels et al. (2019) [48] 37 walk test (ESWT) fatigability during walking
in SMA3
Longitudinal, observational n = 73 13.5 (12.4) range 6MWT Baseline SMA3a 257.1 (107.3)
Montes et al. (2018) [10] 2.6–49.1 SMA3b 390.2 (144.0)
Mean rate of change − 7.8
m/year; p = 0.009
Kennedy et al. Journal of Foot and Ankle Research

Age affects rate of change

< 6 yrs.: 9.8 m/ year; 6–10
yrs.: − 7.9 m/year; 11–19 yrs.:
− 20.8 m/year; > 20 yres: −
9.7 m/year; p = 0.005
Cross-sectional, n = 10 31.2; range, 9– 6MWT 273.4 (45.7); range, 53–492
observational 49
(2020) 13:10

Montes et al. (2014) [49]

Dunaway et al. (2014) [50] n = 15 28.7; range 10– 10 m walk/run 362.13 (29.22) 7.44 (0.84) TUG
49 6MWT 12.97 (2.49) s;
Timed up and go Moderate to good correlation
(TUG) between TUG and 10 m walk/
run (r = 0.691; p = 0.009) and
6MWT (r = − 0.514; p < 0.05)
Longitudinal observational n = 38 14.07 (12.43) 6MWT No change in 6MWD
study 3.4–49.3 12 months
Mazzone et al. (2013) [51]a Baseline 294.91 (127)
12 months 293.4 (141)
Cross-sectional, case SMA3 n = 9 22 6MWT ↓ 6MWD
controlled TD n = 9 4–49 years SMA3 343 m (range
Montes et al. (2011) [9] 267–449)
TD 601 m (range 490–733)
Cross-sectional observational n = 18 15.3(13.3) 6MWT 288.9 (161.9) Median (25th,
Montes et al. (2010) [52] 10 m walk/run Strong correlation 75th %)
between 6MWT and 8.4 (5.4,10.7)
10 m walk/run (r = − 0.87;
p < 0.0001)
CMD Cross-sectional observational n = 25 7.76 (3.02) 10 m self-selected 0.97 (0.26) 0.52–1.36 325.23 (109.85) ↓ physical activity
Hayes et al. (2018) [53] 3.25–13.22 walk speed 150–604 Time inactive, % 80.85 (9.15) Low
6MWT steps, % 33.19 (13.11) Medium
StepWatch activity steps, % 51.15 (9.80) High steps,
monitoring % 16.01 (10.27)
Cross-sectional observational CMD n = 41 CMD 6.8 (3.3) 6MWT ↓ 6MWD
case-controlled (6MWT TD 9.1 (3.1) CMD 258.3 m (SD 176)
Johnson et al. (2016) [54] n = 33) TD 568.3 m (SD 73.2);
Page 8 of 15

TD n = 29 p < 0.001
Table 1 Review papers including disease, author, study type, sample age and size, outcome measures and main findings (Continued)
Disease Study type Sample size Age Outcome measures Gait speed 6MWD 10 m walk/run Other assessments
Author years m/s m s
mean (SD) mean (SD) mean (SD) mean (SD)
FSHD Observational test-retest reli n = 86 49.1 (15.2) 18– 6MWT 404.3 (123.9); Reliability
ability study 84 ICC = 0.99 (n = 25)
Eichinger et al. (2017) [55]a Minimal detectable
change (MDC95) 34.3
Late Observational cross- n = 22 48.6 (range 13– Gait speed 1.02 (0.30) Variable performance 10 m fast walk
onset sectional Gender age- 72) 6MWT ranging from 39.4 to 1.41 (0.42)
Pompe McIntosh et al. (2015) [56]a matched 10 m fast walk test 110% predicted m/s = 7.09 s
reference
data
Collagen Longitudinal observational n = 32 Range 4.8–21.2 6MWT 338.27 (126.65) 144–600 10 m walk
VI Meilleur et al. (2015) [57]a (n = 11 for 10 m walk/run 8.6 (3.5) 4.0–15.8
10 m walk/
run and
6MWT)
Kennedy et al. Journal of Foot and Ankle Research

NMD Cross-sectional observational n = 77 10.1 ± 2.93 6MWT 442.1 (121.6) 2MWD = 149.8 (40.3) m
Witherspoon et al. 2MWT Strong correlation 2MWD
(mixed) (2019) [58] c and 6MWD
r = 0.90, p < 0.01
Cross-sectional observational n = 40 DMD 9.05 (3.1) 6MWT DMD 349.70 (77.18) TUG
Kaya et al. (2015) [59] DMD = 20 PN 12.95 (3.3) TUG PN 358.85 (75.07) DMD 7.79 (1.54) s
(2020) 13:10

PN d = 20 NS PN 10.13 (2.63) s
p < 0.01
Cross-sectional observational n = 114 21.3 (range 4– 6MWT Mean 61.9%
Montes et al. (2013) [60] a e 64) (% predicted of DMD/BMD 65.1%
normative reference SMA 52.0%
data) myasthenia gravis 66.3%
GLUT1 deficiency/mitochondrial
disorders 63.9%
Cross-sectional observational n = 17 Median (IQR) 6MWT Median (IQR) 485 (131) Activity monitor
Holtebekk (2013) [61] f 14.2 (3.6) Activity monitoring Moderate physical activity
SenseWear Armband Median (IQR) 2.4 (1.9) hours/
weekday
1.1 (3.3) hours/weekend day
Mean and standard deviation (SD) unless otherwise stated; IQR = inter-quartile rank; Main findings in bold
Abbreviations: 6MWT six-minute walk test, 6MWD six-minute walk distance, BMD Becker muscular dystrophy, BOT-2 Bruininks-Oseretsky Test, 2nd Edition, CMT Charcot-Marie-Tooth disease, CMD Congenital myotonic
dystrophy, DMD Duchenne muscular dystrophy, ESWT Endurance shuttle walk test, FMS Functional Mobility Scale, FSHD fascioscapulohumeral dystrophy, LGMD limb girdle muscular dystrophy, NMD neuromuscular
disease, norm norm, PN peripheral neuropathies, SMA spinal muscular atrophy
a
Nelson - included adult participants with no sub analysis; McIntosh – 2 of 22 subjects aged ≤18 years, no sub-analysis; Mazzone - included adult participants with no sub analysis; Eichinger – one 18-year-old
participant, all others adults with no sub-analysis; Meilleur - included adult participants with no sub analysis; Montes - included adult participants with no sub analysis
b
same data sets
c
Collagen VI-related dystrophy (COL6-RD), laminin alpha 2-related dystrophy (LAMA2-RD), limb-girdle muscular dystrophy (LGMD), and RYR1-related myopathies (RYR1-RM), and other
d
PN = peripheral neuropathies including CMT/hereditary motor and sensory neuropathy (HMSN), motor neuropathy (MN) and polyneuropathy (PNP)
e
Spinal muscular atrophy (n = 23), Duchenne/Becker muscular dystrophy (n = 29), myasthenia gravis (n = 12), or an energy failure syndrome (glucose transporter protein type 1 [GLUT1] deficiency/mitochondrial
disorders) (n = 50)
f
CMT n = 4, Congenital myopathy n = 2, LGMD 2I n = 8, BMD n = 1, Unspecified n = 2
Page 9 of 15
Kennedy et al. Journal of Foot and Ankle Research (2020) 13:10
Gait speed
For this review we focused on gait speed in terms of its
clinical utility as an indicator of health and disability [4, 5].
Assessment of gait speed was diverse with a range of re-
ported methodologies including 3-D gait analysis, elec-
tronic walkway and timed distance. Typically, gait is
assessed at natural self-selected steady walking pace, how-
ever some studies reported gait speed as calculated from
the 10 m walk/run, usually a fast walk or run test [27, 56].
Gait speed was described most often in studies of children
with CMT (ten of fifteen papers), a reflection of the use of
clinical gait analysis in preparation for orthopaedic surgery
for the management of foot deformities common in CMT
[11, 16, 18–21, 23–26]. Children with CMT walked more
slowly than their typically developing peers and a decline
in gait speed over time was evident when growth was
accounted for by normalising gait speed to height or leg
length [16]. Greater disability in children with CMT was
reflected in slower gait speed in more severely affected
children [19].
Younger boys (< 7 years) with DMD did not walk sig-
nificantly slower than their typically developing peers
[41, 45]. However, boys older than 8 years with DMD
were significantly slower than their peers, an indicator of
the relentless and degenerative muscle disease [8, 31].
The study by Doglio et al. (2011) was the only study to
normalise gait speed to height when comparing boys
with DMD to TD controls. Normalising gait parameters
is an important consideration for boys with DMD who
are typically treated with corticosteroids, of which
growth retardation is a known side-effect. Therefore,
steroid-treated boys with DMD tend to be smaller than
their age-matched, steroid naïve and non-affected peers
[69]. Normalisation to height and/or leg length is an im-
portant to factor when reporting gait speed in paediatric
populations [70, 71].
Gait speed was reported in two other studies in chil-
dren with CMD [53] and a mixed aged study of children
and adults with late-onset Pompe disease [56]. Whilst
neither study included unaffected controls, the reported
gait speed for both cohorts was considerably slower than
reported normative reference data [72].
Six-minute walk test
The 6MWT is a valid and reliable standardised test of
physical endurance in boys with DMD [38]. A test of
ambulatory capacity, the 6MWT measures distance
walked in six minutes. Developed from the American
Thoracic Society and FDA-approved 6MWT [64], the
test has been modified for children with NMD with the
addition of a safety chaser and standardised verbal en-
couragement [44]. The utility of the 6MWT in paediatric
NMD clinical research is evident with over half of
the studies included in this review reporting its use
Page 10 of 15
[9–11, 14, 16, 17, 24, 25, 29, 32–35, 37–40, 42–44,
50–61] (Table 1). Typical walkway distances were re-
ported as 25 m however some studies used walkways
as short as 10 m [24, 25]. This may reduce distance
walked due to more frequent turns resulting in
greater time spent decelerating and less time at a fast
walking pace [73].
Six-minute walk distance (6MWD) is reduced in chil-
dren and adolescents with NMD when compared to typic-
ally developing controls or normative reference data. In
boys with DMD and children with SMA type 3 and CMT,
6MWD declines with increasing age, reflecting disease
progression and increasing disability [10, 16, 34, 35, 37,
39, 40]. Normalisation of 6MWD to height or leg length,
accounts for linear growth across age groups and in longi-
tudinal studies, and is an important factor when determin-
ing the effect of disease on function [16]. Burns and
colleagues (2009), demonstrated a trend to shorter
6MWD in older children [25]. In a further study over 12
months, normalisation of 6MWD accounting for growth
revealed a decline in ambulatory capacity in children with
CMT [16]. Genotype also affects ambulatory capacity in
the 6MWT; children with milder subtypes of CMT in a
large study of 520 participants, walked further than chil-
dren with more severe subtypes [17]. Deterioration in am-
bulatory capacity over time was also affected by genotype
in 80 boys with DMD [40]. Several studies have reported
rates of change, either minimally clinically important dif-
ference (MCID) or minimal detectable change (MDC) for
6MWD in different NMD including DMD (MCID 26.4–
31.7 m; − 53.67 change over 12 months) [37, 38], SMA (−
7.9 to − 9.7 m over 12 months) [10] and FSHD (MDC95
34.3 m) [55]. Measures of rate of change, MCID or MCD
are useful for clinicians when comparing the ambulatory
function of the children in their own clinical practice.
Timed function tests – 10 m walk/run
The timed 10 m walk/run is widely used to assess function
in NMD and is a sensitive measure of disease progression
in ambulant boys with DMD [62, 74, 75]. In clinical prac-
tice, the timed 10 m walk/run is conducted as a fast walk
or run dependent on the abilities of the child. However, in
the literature there were differences noted between
whether the test was conducted as a timed walk [15, 41,
56, 57] or run, and earlier studies conducted the test over
30 ft or 9 m [46, 47]. Timed 10 m walk/run was most often
reported in boys with DMD [27, 29, 36–39, 41–43, 46, 47]
reflecting its common use as a predictor of disease in
DMD and less frequently in studies of CMT, SMA, Pompe
and Collagen VI [11, 15, 50, 52, 56, 57]. Across all NMDs,
10 m walk/run times were slower compared to controls or
reported normative reference ranges. Disease progression
in boys with DMD was demonstrated with several studies
Kennedy et al. Journal of Foot and Ankle Research (2020) 13:10
reporting slower speed over 10 m in boys older than 7
years [36, 39, 42].
Other assessments
Assessments of balance, endurance and alternative dis-
tance and timed tests (100 m timed walk and two-
minute walk test) were reported less frequently. The bal-
ance subset of the Bruininks-Oseretsky Test of Motor
Proficiency, 2nd Ed (BOT-2, NCS Pearson, Upper Saddle
River, NJ, USA) is a ten-item standardised test of bal-
ance in standing and walking [65]. It is widely used in
paediatric CMT having been incorporated into the
disease-specific CMT Pediatric Scale (CMTPedS) [76].
Balance in children with CMT was significantly reduced
when compared to age- and gender-matched controls
and normative reference data [11, 13, 14]. However,
over 12 months’, balance did not significantly deterior-
ate, indicative of the relatively slow progression of
neuropathy in children with CMT [16]. Reduced bal-
ance (BOT-2) was associated with wider base of sup-
port and greater step-to-step variability in the gait of
children with CMT [11].
The TUG was reported in two studies and is a valid,
reliable and responsive measure of gait-related balance
in children with physical disabilities [50, 59, 77, 78]. It
measures the time taken to stand from a seated position,
walk 3 m, turn around and return to a seated position.
Dunaway and colleagues (2014) demonstrated an associ-
ation between the TUG, slower 10 m walk/run time and
shorter 6MWD in children with SMA type 3 [50]. In a
further study comparing older children with peripheral
neuropathies (PN) of mixed origin to younger boys with
DMD, TUG times were longer in the children with
mixed PN [59]. The authors attributed the difference be-
tween groups to the effects of distal versus proximal
weakness patterns, however it may have also been due to
the PN group being older and therefore likely to be
more affected by their disease. Both the BOT-2 and the
TUG are useful assessments of gait-related balance and
inform clinical interpretation of the effects of NMD on
gait and function.
Alternatives to the 6MWT were reported in two stud-
ies. Alfano and colleagues (2017) reported the develop-
ment and validation of a 100 m timed test in boys with
DMD as an assessment of functional ambulatory per-
formance. Their study included the establishment of typ-
ically developing normative reference data [30]. Findings
from this study indicated that performance on the 100 m
timed test improved up to the age of 7 years before plat-
eauing and declining with increasing age [30]. This find-
ing is similar to the 10 m walk/run and the 6MWT in
boys with DMD and is reflective of disease progression
[36, 39, 40, 42]. A second study in children with mixed
NMD, reported a two-minute walk distance (2MWD)
Page 11 of 15
derived from the two-minute mark of the standard
6MWT, and found a strong correlation between 2MWD
and 6MWD [58]. Both the 100 m timed test and the
2MWT may offer realistic alternatives to the longer
6MWT, especially in children with behavioural and at-
tentional problems who may find the time and testing
constraints of six minutes challenging.
The 6MWT and more recently the 100 m timed test
and 2MWT, are all described as tests of physical endur-
ance in paediatric NMD and as surrogate measures of
physical fatigue in DMD, SMA and CMT [9, 25, 44].
Bartels and colleagues (2019) have recently described the
concept of fatigability in SMA, that is, “the inability to
perform prolonged repetitive tasks during activities of
daily life”, and have developed a group of endurance
tests to assess fatigability [48]. The Endurance Shuttle
Walk Test is a feasible test of endurance in ambulant
people with SMA type 3. An externally paced walking
task, the objective is to cover 10 m before each beep.
The time between repeated beeps decreases, requiring
an incremental increase in walking speed. This pilot
study is the first report of the Endurance Shuttle Walk
test and further studies are required to determine its val-
idity, responsiveness and clinical utility in SMA and
paediatric NMD.
The advent of wireless wearable activity monitors al-
lows remote measurement of gait-related physical activ-
ity in children with NMD. Several studies have included
wearable devices to measure steps and physical activity
in DMD, CMD and mixed NMD [27, 32, 53, 61]. David-
son and colleagues (2015) found that boys with DMD
have reduced daily step counts and reduced high activity
time, with correspondingly greater inactivity compared
to typically developing peers [32]. In a longitudinal
study, Fowler and colleagues (2018) described physical
activity levels in boys with DMD following a similar tra-
jectory to timed tests and the 6MWT [27]. Daily step
counts rose up to the age of 8 years, before plateauing
and declining from the age of 10 years [27]. Children
with NMD are largely inactive, spending up to 80% of
their awake time in sedentary activities and on average
only 2 h a day at a moderate intensity of activity [53, 61].
Whilst we assume neuromuscular weakness contributes
to reduced physical activity, it is quite possible that re-
duced physical activity contributes further to increasing
weakness. Lack of physical activity, together with
disease-related weakness, is likely to impact gait and
function in children with NMD.
Descriptive measures of gait
Together with quantitative measures of gait and func-
tion, descriptive scales and questionnaires are used to
characterise gait and functional ambulation in paediatric
NMD. Two such measures reported in this review are
Kennedy et al. Journal of Foot and Ankle Research (2020) 13:10
the Functional Mobility Scale (FMS) [67] and the Walk-
12 [68] which have not been widely utilised in paediatric
NMD to date.
The Functional Mobility Scale (FMS) is a clinical tool
used to classify typical mobility over three distance cat-
egories – 5, 50 and 500 m in children with gait dysfunc-
tion [67]. These distances are commensurate with
walking in the home (5 m), between classrooms in the
school environment (50 m) and distances required in
general community environments (500 m). The scale
considers the level of assistance the child requires and a
grading from 1 to 6 is applied; where 1 indicates the use
of a wheelchair and 6 indicates fully independent walk-
ing on all surfaces and terrains, including stairs without
use of a rail. One study has described functional mobility
in children with CMT [16]. In this study 78% of the chil-
dren reported reduced ambulatory function, across one
or all distance/environment categories (score < 6) de-
scribing the functional impact of disease. Over 12
months there was little change in FMS scores, in keeping
with the slow progression of CMT.
The Walk-12 is a self-reported questionnaire of per-
ceived impact of disease on gait and gait related activ-
ities, such as running, using stairs and balance, modified
and validated in adults with peripheral neuropathies [68,
79]. The tool is scored from 0 to 100%, where 0% indi-
cates no impact and 100% indicates a high impact of dis-
ease on gait and related activities. In two studies, Walk-
12 scores ranged from 12 to 25%, indicating that chil-
dren with CMT perceived only mild impact of disease
on gait and gait-related function [14, 22]. Interest-
ingly, further examination of answers to individual
questions indicated that CMT affected their ability to
run (43%), ascend or descend stairs (41%), the speed
with which they could walk (31%) and made it more
effortful to walk (31%) [14]. Additionally, over 40% of
the children reported moderate to severe limitations
to their ability to walk longer distances in their every-
day environments.
Clinical implications and future directions
Gait performance and functional ambulation are bio-
markers of disease severity in paediatric NMD, providing
a measure of disability. Assessment of gait and func-
tional ambulation are important outcome measures in
the toolbox of assessments for clinical research trials
and in the clinical setting. With the advent of disease-
modifying pharmacological treatments and uptake of
physiotherapeutic exercise, younger people, including
children with NMD are likely to benefit most from treat-
ments. Therefore, it is important to utilise functional
measures specific to children and adolescents to monitor
disease progression and treatment efficacy.
Page 12 of 15
There remains a need for further research and devel-
opment of functional gait outcome measures for paediat-
ric NMD. Limitations including the heterogeneity of the
study populations and differences in assessment proto-
cols precluded meta-analysis of these studies. As evi-
dence accumulates, a more analytical systematic review
may provide additional insights. The disparity of gait as-
sessments in paediatric neuromuscular diseases also sug-
gests that a Delphi survey would be useful in
establishing expert consensus on which measures to use.
Factors such as the normalization of gait parameters is
important when comparing gait across age ranges and
longitudinally to account for growth in children and
should be standardly applied both clinically and in re-
search. Further development and publication of paediat-
ric normative reference datasets and MCIDs will be a
valuable resource for clinicians working in neuromuscu-
lar clinics. Qualitative characterisation of gait and func-
tional ambulation with scales or questionnaires enables
clinicians to gain an understanding of the effect of dis-
ease on the day-to-day lives of children with NMD, be-
yond the neuromuscular outpatient clinic. The self-
reported scales of functional mobility and gait-related
activities require validation in paediatric NMD popula-
tions to ensure that they provide meaningful information
and enable greater uptake by clinicians. Further explor-
ation and utilization of technology for remote and wire-
less monitoring and measurement of walking in the
typical environments of children, including home, school
and the community provide greater understanding of
the effect of disease on function.
Conclusion
This narrative review has highlighted clinical measures
of gait ranging from gait speed to tests of ambulatory
capacity, physical endurance and gait-related balance
that can be conducted in clinical and research settings
with relative ease. Consideration of environmental fac-
tors affecting function including distance requirements
necessitated by school and community settings is im-
portant when understanding the effect of disease. An in-
dividual’s perception of the effect of disease on walking
and everyday function are important considerations in
the clinical setting. Person-centred characterization and
assessment of gait dysfunction discussed in this narrative
review provides a rich and holistic illustration of disabil-
ity, and offers genuine outcome measures of potential
therapeutic benefits on gait and functional ambulation
in paediatric NMD. However, consensus is required
amongst experts in paediatric neuromuscular disorders
to establish a core set of gait and functional ambulatory
assessments that can be used clinically and in research
settings.
Kennedy et al. Journal of Foot and Ankle Research (2020) 13:10
Supplementary information
Supplementary information accompanies this paper at https://doi.org/10.
1186/s13047-020-0378-2.
Additional file 1. Search strategy for narrative review “Walking and
weakness in children: a narrative review of gait and functional
ambulation in paediatric neuromuscular disease”.
Acknowledgements
The authors would like to thank the wider neuromuscular clinical and
research community who contribute to a rich resource of publicly available
knowledge in a field of rare diseases.
Authors’ contributions
RK concept, review of the literature, drafted manuscript; KC – review of
literature and reviewed draft manuscript; JM – reviewed draft manuscript; KP
– concept and reviewed draft manuscript. All authors contributed to the
writing and approved the final manuscript.
Funding
None.
Availability of data and materials
All articles cited in this review are accessible through article repositories and
journal websites.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Author details
1
Department of Neurology, The Royal Children’s Hospital, Parkville, Vic,
Australia. 2Murdoch Children’s Research Institute, Parkville, Vic, Australia.
3
Department of Physiotherapy, The University of Melbourne, Parkville, Vic,
Australia.
Received: 23 November 2019 Accepted: 18 February 2020
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